Influx Mechanism of 2′,3′-Dideoxyinosine and Uridine at the Blood-Placenta Barrier
Influx Mechanism of 2′,3′-Dideoxyinosine and Uridine at the Blood-Placenta Barrier
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DOI：
10.1016/j.placenta.2008.11.022
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发表时间：
2009-03-01
期刊：
影响因子：
3.8
通讯作者：
Nakashima, E.
中科院分区：
文献类型：
--
作者：
Sato, K.;Sai, Y.;Nakashima, E.
血-胎盘屏障(BPB)用于保护胎儿免受毒素的影响，并将包括核苷和激素在内的各种营养物质从母亲体内输送到胎儿体内。已知核苷转运体有助于核苷及其类似物的转移。2‘，3’-二脱氧肌苷(2‘，3’-dideoxinosine，DDI)具有核苷结构，与BPB交叉。虽然DDI是几种转运蛋白的底物，包括平衡核苷转运蛋白(ENT1和ENT2)，但DDI在胎盘中的转运机制尚未确定。因此，本研究的目的是阐明DDI从母体到胎儿的流入机制，并研究DDI和尿苷在BPB的转运之间的相互作用。我们用条件永生化的大鼠合体滋养层细胞系tr-TBT 18d-1作为BPB模型，研究DDI和尿苷的摄取。DDI的吸收依赖于温度，不依赖于Na+，并且是饱和的。动力学分析得出DDL和尿苷的K-m值分别为6.51 mm和23.4µM。尿苷摄取被ENT1和ENT2底物抑制，底物或抑制剂在抑制ENT2的浓度时也抑制DDI摄取。表达大鼠ent2基因的非洲爪哇卵母细胞对尿苷的摄取被5 mM DDI抑制，这与tr-TBT 18d-1的结果一致。我们的结果表明，在TR-TBT 18d-1细胞中，DDL和尿苷都部分通过ent2被摄取，因此ent2可能有助于它们在BPB的摄取。(C)2008爱思唯尔有限公司。保留所有权利。
The blood-placenta barrier (BPB) serves to protect the fetus from exposure to toxins, and to transport various nutrients, including nucleosides, and hormones from mother, to fetus. It is known that nucleoside transporters contribute to the transfer of nucleosides and nucleoside analogues. 2',3'-Dideoxyinosine (ddI) has a nucleoside structure, and crosses the BPB. Although ddI is a substrate of several transporters, including equilibrative nucleoside transporters (ENT1 and ENT2), the transport mechanism of ddI in the placenta has not yet been characterized. Therefore, the purpose of this Study was to clarify the influx mechanisms of ddI from the maternal to the fetal side, and to examine the interaction between ddI and uridine transport at the BPB. We Studied ddI and uridine uptakes using a conditionally immortalized rat syncytiotrophoblast cell line, TR-TBT 18d-1, as a BPB model. The ddI uptake was temperature-dependent, Na+-independent and saturable. Kinetic analysis yielded K-m values for ddl and uridine of 6.51 mM and 23.4 mu M, respectively. Uridine uptake was inhibited by ENT1 and ENT2 substrates, and ddI uptake was also inhibited by substrates or inhibitors at concentrations that inhibit ENT2. uridine uptake in Xenopus laevis oocytes expressing rat ENT2 was inhibited by 5 mM ddI, in agreement with the results for TR-TBT 18d-1. Our results indicate that ddl and Uridine are both taken LIP in part via ENT2 in TR-TBT 18d-1 cells, and therefore that ENT2 may contribute to their uptake at the BPB. (C) 2008 Elsevier Ltd. All rights reserved.